1-209693771-A-G

Position:

• chr1-209693771-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181755.3(HSD11B1):​c.-27+7486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.899 in 152,268 control chromosomes in the GnomAD database, including 61,867 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61867 hom., cov: 32)
• Consequence: HSD11B1 NM_181755.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

Genes affected

HSD11B1 (HGNC:5208): (hydroxysteroid 11-beta dehydrogenase 1) The protein encoded by this gene is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. In addition, the encoded protein can catalyze the reverse reaction, the conversion of cortisone to cortisol. Too much cortisol can lead to central obesity, and a particular variation in this gene has been associated with obesity and insulin resistance in children. Mutations in this gene and H6PD (hexose-6-phosphate dehydrogenase (glucose 1-dehydrogenase)) are the cause of cortisone reductase deficiency. Alternate splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, May 2011]

HSD11B1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD11B1	NM_001206741.2	c.-49+7486A>G		intron_variant			NP_001193670.1
HSD11B1	NM_181755.3	c.-27+7486A>G		intron_variant			NP_861420.1
HSD11B1-AS1	NR_134509.1	n.96+30259T>C		intron_variant
HSD11B1-AS1	NR_134510.1	n.67-30710T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD11B1	ENST00000367028.6	c.-49+7486A>G		intron_variant		5		ENSP00000355995.1
HSD11B1	ENST00000261465.5	c.-49+7486A>G		intron_variant		5		ENSP00000261465.2
HSD11B1	ENST00000615289.4	c.-27+7486A>G		intron_variant		5		ENSP00000478430.1
HSD11B1-AS1	ENST00000441672.1	n.96+30259T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.899 AC: 136711 AN: 152150 Hom.: 61825 Cov.: 32

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.852

Gnomad ASJ AF: 0.959

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.953

Gnomad OTH AF: 0.903

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.899 AC: 136813 AN: 152268 Hom.: 61867 Cov.: 32 AF XY: 0.897 AC XY: 66767 AN XY: 74444

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.852

Gnomad4 ASJ AF: 0.959

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.976

Gnomad4 NFE AF: 0.953

Gnomad4 OTH AF: 0.903

Alfa AF: 0.936 Hom.: 43052

Bravo AF: 0.889

Asia WGS AF: 0.786 AC: 2735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.082
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10082248; hg19: chr1-209867116;